Niemann-Pick Type C (NPC) disease is a lipid storage disorder that is characterized by progressive hepatomegaly and neurodegeneration. In this condition, lipids accumulate in the liver, kidney, spleen, bone marrow and brain. The cause of NPC is NPC1 or NPC2 gene mutation which induces the accumulation of unesterified cholesterol in the late endosomes/lysosomes.
NPC2 is a small soluble glycoprotein containing 151 amino acids, which was first characterized as a major secretory protein in human epididymis. NPC2 protein interacts with cholesterol in lysosomes to maintain the homeostasis of cholesterol in the body. In addition, in humans and mice, NPC2 is expressed in the liver and secreted into bile (Klein, Amigo et al. 2006). When NPC2 gene mutates, cholesterol will accumulate in the cell (Frolov, Zielinski et al. 2003). In addition, it has been reported that Asn-38 is never glycosylated, while Asn-58 and Asn-138 can be glycosylated. Under normal conditions, some NPC2 proteins are glycosylated only on Asn-58, and others are glycosylated both on Asn-58 and Asn-138. The Asn-58 modification is suggested to be necessary for proper NPC2 targeting to lysosomes, while the Asn-138 is non-essential. Although all glycoforms are able to bind cholesterol, one report indicated an aberrant glycosylation pattern for NPC2 in NPC1 deficient mouse livers and suggested that the cholesterol transport deficiency in NPC1 disease may arise from defects of glycosylated forms of NPC2 protein (Chikh, Vey et al. 2004).
In 1975, the method of producing “monoclonal antibody” was developed. The antibodies are mono-specific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell. Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. Production of monoclonal antibodies involve human-mouse hybrid cells. Monoclonal antibodies are typically made by fusing myeloma cells with the spleen cells from a mouse that has been immunized with the desired antigen.
How to produce a huge amount of anti-NPC2 monoclonal antibodies and detect cancer by these antibodies is a problem to be solved.